VITSA: Mapping Virus Host Interactions using the Cellular Thermal Shift Assay

To complete their replication cycles viruses must reprogram cellular pathways in order to transform cells to becoming virus factories. Similarly, cells can rapidly react to infection, activating cell-intrinsic innate immune pathways.

Due to the awesome complexity of the cell, it has been challenging to get a comprehensive picture of the changes that occur early in infection.

We propose to develop the Cellular Thermal Shift Assay (CETSA) to study changes in the interaction states of the proteome of cells infected with different RNA viruses or stimulated with molecules for activating cell-intrinsic defences.

Our preliminary experiments have detected significant CETSA profile changes for hundreds of cellular proteins in only very short times of infection with Semliki Forest virus and with SARS-CoV-2.

Several of these protein had previously been shown to be important for infection, but most are novel, confirming that interactions of importance can be detected using this approaches.

During the course of this project, we propose to apply this technology to uncovering interactions critical for viral pathogenesis and for cellular resistance to infection.

The transformative potential of the VITSA project and the synergies from the two complementary groups will allow us to efficiently address these fundamental questions.

We are thus convinced that the VITSA collaboration will open up many new avenues of exploration for our own work, and that of our collaborators.